1. Field of the Invention
The present invention relates to a method for the production of an in vivo lung metastatic hepatoma model, which may be useful in the search for and evaluation of antimetastatic agents.
2. Background of the Invention
Metastasis is one of the most malignant phenotypic expressions of carcinoma, and the inhibition of metastasis is the ultimate goal of anticancer therapy.
However, current antimetastatic studies using in vivo models, that is, animal models, have metastasis produced through an extremely artificial process. For example, tumor tissue itself or tumor cells have been administered by subcutaneous or intraperitoneal injection, or via direct intravenous injection to nude mice, i.e., animals whose rejection immunity is artificially removed or weakened. It is clear, however, that individual defense mechanism such as immunopotency or drug pharmacokinetics change according to the developmental stage of primary lesion or degree of systemic distribution of tumor tissue in individuals. Thus, the establishment of an animal model which represents the natural course of carcinoma in the human body, that is, an animal model where metastasis would be formed after development of carcinoma, has been highly desired.
Nevertheless, there is currently no such animal model that represents the natural course of carcinoma in the human body, that is, an animal model where lung metastasis would be formed after development of hepatoma with great efficiency. Accordingly, such an animal model would be extremely useful in the development of anticancer therapies.
It an object of the present invention to provide a model which represents the natural course of carcinoma in the human body, that is, an animal model where metastasis are formed after development of carcinoma.
The object of the present invention may be accomplished with a method of producing an in vivo model of lung metastatic hepatoma, comprising administering an effective amount of at least one nitroso compound to an animal for a time sufficient to produce lung metastatic hepatoma in the animal.
In the inventive method, administration of the hepatic carcinogen, i.e., nitroso compounds, to the animals allows induction of hepatoma in animals with great efficiency. Moreover, the present invention provides for metastasis formation in the lung after development of hepatoma. In other words, the obtained model is a metastasis model which represents the natural course of carcinoma where the whole host reactions in the host body against carcinoma are incorporated including development of hepatoma and metastasis formation. Thus, the model provided by the method of the present invention is a useful model to determine the inhibitory effect on lung metastasis of hepatoma.
Thus, the present invention can provide, with great efficiency, a model which may allow elucidation of mechanism of carcinoma metastasis in the body from more practical view points. Moreover, evaluation of the effect of the host on tumor cells and adverse effects on other organs allow development of antimetastatic agents which can be readily applicable to clinical practices.
As described above, the present invention provides a method for the production of in vivo lung metastatic hepatoma model which allows not only development of hepatoma and formation of lung metastasis with great efficiency but also evaluation of metastasis modification effect during the period of lung metastasis formation of hepatoma.